We propose to study chronic diseases of the central nervous system (CNS) on the premise that some of these diseases are viral-induced. Brain suspensions from patients with representative CNS diseases, kuru and Creutzfeldt-Jakob disease, will be inoculated intracerebrally, intraperitoneally, and intravenously into marmosets, South American nonhuman primates. The etiology and pathogenesis of the experimentally induced diseases will be studied by viral isolation techniques, including long term brain explant cultures, serial animal transmissions, light and electron microscopy, histochemistry and immunological techniques for the demonstration of new antigens, circulating antibodies and cell-mediated immune responses. Kuru and Creutzfeldt-Jakob disease have been transmitted to marmosets and serial marmoset to marmoset passage has shortened the incubation period to an average of 7-8 months. In addition, one marmoset kuru brain explant culture, 30th tissue culture passage, has been found to contain a "C-type virus" as demonstrated by electron microscopic study and by reverse transcription activity. The availability of a susceptible experiment animal model characterized by a short incubation period will permit more rapid progress toward characterizing the infectious agent and defining the pathogenetic mechanism(s) of this disease, using the general approaches as listed above.